LabCorp and its Specialty Testing Group, a fully integrated portfolio of specialty and esoteric testing laboratories.
To help diagnose rheumatoid arthritis (RA) and differentiate it from other types of arthritis; to help evaluate the prognosis of a person with RA
When a healthcare practitioner suspects RA in someone who has joint inflammation with symptoms such as pain, stiffness, limited motion, and swelling in multiple joints
A blood sample drawn from a vein in your arm
Tell your healthcare practitioner about any medications and/or supplements you are taking. You may be instructed to stop taking multivitamins or dietary supplements containing biotin (vitamin B7) at least 8 hours before the blood draw.
Cyclic citrullinated peptide antibodies are autoantibodies produced by the immune system that are directed against cyclic citrullinated peptides (CCP). This test detects and measures anti-CCP antibodies in the blood.
Citrulline is naturally produced in the body as part of the metabolism of the amino acid arginine. However, in joints with rheumatoid arthritis (RA), this conversion may occur at a higher rate. Citrulline changes the protein structure and can trigger an immune response, producing autoantibodies against joint proteins. The CCP antibody test helps to diagnose RA and can be useful in identifying people with a more rapidly erosive form of the disease.
RA is a chronic, systemic autoimmune disease that causes inflammation, pain, stiffness, and destructive changes in the hands, feet, and other joints throughout the body. It can affect anyone at any age, but it usually develops between the ages of 40 and 60, and about 75% of those affected are women. The course of RA and its prognosis are variable. It may develop and progress slowly or rapidly. It may go into remission in some people and, in a few, it may go away. Left untreated, RA can shorten a person's lifespan and can, within a few years, leave many of those affected too disabled to work.
There are a variety of treatments available to minimize the complications of RA, but they depend on making an accurate diagnosis and on beginning treatment before the development of irreversible joint damage. Rheumatoid factor (RF) has been the primary blood test used to detect RA and distinguish it from other types of arthritis and other inflammatory processes. However, the sensitivity and specificity of RF are not ideal; it can be negative in people who have clinical signs of RA and positive in people who do not. Studies have shown that the CCP antibody test has a similar sensitivity to RF but a much higher specificity (95-98%) and is more likely to be positive with early RA.
The 2010 Rheumatoid Arthritis Classification Criteria from the American College of Rheumatology (ACR) includes CCP antibody testing, along with RF, as part of its criteria for diagnosing rheumatoid arthritis. According to the ACR, CCP antibodies may be detected in about 50-60% of people with early RA, as early as 3-6 months after the beginning of symptoms. Early detection and diagnosis of RA allows healthcare providers to begin aggressive treatment of the condition, minimizing the associated complications and tissue damage.
A cyclic citrullinated peptide (CCP) antibody test may be ordered along with or following a rheumatoid factor (RF) test to help diagnose rheumatoid arthritis (RA) and to assess the severity and probable course of the disease (prognosis).
CCP antibody testing may also be ordered to help evaluate the likely development of RA in people with undifferentiated arthritis – those whose symptoms suggest but do not yet meet the American College of Rheumatology (ACR) criteria for RA. According to ACR, approximately 95% of those with a positive CCP antibody will meet the criteria of RA in the future. Early detection of RA is essential for guiding treatment decisions.
A CCP antibody test is primarily ordered along with an RF test when someone has signs and symptoms that may be due to previously undiagnosed inflammatory arthritis or has been diagnosed with undifferentiated arthritis. It may be ordered as a follow-up test to a negative RF test when clinical signs and symptoms lead a healthcare practitioner to suspect RA. RA usually affects multiple joints symmetrically. Signs and symptoms may include:
When people with signs and symptoms of arthritis are positive for both CCP antibody and RF, it is very likely that they have RA and it is likely that they may develop a more rapidly progressive and severe form of the disease. When people are positive for CCP antibody but not RF, or have low levels of both, and have clinical signs that suggest RA, then it is likely that they have early RA or that they will develop RA in the future.
When individuals are negative for CCP antibody but have a positive RF, then the clinical signs and symptoms are more vital in determining whether they have RA or some other inflammatory condition. When someone is negative for both CCP antibody and RF, then it is less likely that the person has RA. It must be emphasized, however, that RA is a clinical diagnosis and may be made in the absence of positive tests for autoantibodies.
The CCP antibody test is relatively new. It is becoming more widely used but is still less frequently ordered than the RF test.
CCP antibodies are rarely found in other autoimmune conditions, such as lupus, Graves disease and Sjogren syndrome, and may be detected in infections such as tuberculosis.
No. CCP antibody is not recommended as a screening test. Like RF, it is best used to evaluate individuals whose clinical signs suggest RA or who have already been diagnosed with undifferentiated arthritis.
Anti-CCP testing is widely available and may be tested for by your physician. This test may not be available in all laboratories but can be routinely sent to a reference laboratory.
Like other autoantibodies, once developed by the body's immune system, levels of CCP antibodies may fluctuate over time but will not go away. CCP antibody levels may decrease with treatment.
Your healthcare provider may choose to order an ESR and/or CRP, tests that detect inflammation. The healthcare practitioner may also order a complete blood count (CBC) to check for a high white blood cell count, another sign of inflammation, and to check for anemia, a condition common in people with RA. For added information, an analysis of joint fluid (synovial fluid) may be performed. In addition, your healthcare provider may also order antinuclear antibody (ANA) testing. A negative ANA helps exclude lupus and other systemic rheumatic diseases; the ANA may be positive in up to one-third of patients with RA.
Sources Used in Current Review
2019 review completed by Xiaochun Zhang, PhD, DABCC, DABMLI, HCLD, Pathology and Laboratory Medicine, Cleveland Clinic.
American College of Rheumatoid. Glossary: Cyclic citrullinated peptide (CCP) antibody test. Available online at https://www.rheumatology.org/Learning-Center/Glossary/ArticleType/ArticleView/ArticleID/439. Accessed on 01/19/2019.
(0//23/2018) PJW Venables, Ravinder N Maini. Section Editor: James R O'Dell. Deputy Editor: Paul L Romain. Diagnosis and differential diagnosis of rheumatoid arthritis – UpToDate. Available online at https://www.uptodate.com/contents/diagnosis-and-differential-diagnosis-of-rheumatoid-arthritis#H8594869. Accessed on 01/19/2019.
Holmes EW, Samarasinghe S, Emanuele MA, Meah F. Biotin Interference in Clinical Immunoassays: A Cause for Concern. Arch Pathol Lab Med. 2017 Nov;141(11):1459-1460. doi: 10.5858/arpa.2017-0107-LE.
Grimsey P, et al. Population pharmacokinetics of exogenous biotin and the relationship between biotin serum levels and in vitro immunoassay Interference. 2017;2: 247–256. International Journal of Pharmacokinetics.
Sources Used in Previous Reviews
Thomas, Clayton L., Editor (1997). Taber's Cyclopedic Medical Dictionary. F.A. Davis Company, Philadelphia, PA [18th Edition].
Pagana, Kathleen D. & Pagana, Timothy J. (2001). Mosby's Diagnostic and Laboratory Test Reference 5th Edition: Mosby, Inc., Saint Louis, MO.
Shiel, W. (2004 September 17, Reviewed). Citrulline Antibody. MedicineNet.com [On-line information]. Available online at http://www.medicinenet.com/citrulline_antibody/article.htm.
Check, W. (2003 June). Assay takes arthritis out of the gray zone. College of American Pathologists, Feature Story [On-line journal]. Available online at http://www.cap.org/apps/docs/cap_today/feature_stories/rheumarthritis_assay.html.
Bizzarola, N. et. al. (2001). Diagnostic Accuracy of the Anti-Citrulline Antibody Assay for Rheumatoid Arthritis. Clinical Chemistry. 2001; 47:1089-1093. [On-line information]. Available online at http://www.clinchem.org/cgi/content/full/47/6/1089.
(2004 February 4, Updated). Cyclic Citrullinated Peptide (CCP): A New Serum Marker for Rheumatoid Arthritis. Foundation for Blood Research, Fact Sheet [On-line information]. Available online at http://www.fbr.org/publications/factsheets/fs-ccp.html.
Wiik, A., et. al. (2003). The Use of Anti-cyclic Citrullinated Peptide (anti-CCP) Antibodies in RA. American College of Rheumatology, Hotline [On-line article]. Available online at http://www.rheumatology.org/publications/hotline/1003anticcp.asp.
McCoy, T. (2003 October 24). Simple Blood Test May Predict The Development Of Rheumatoid Arthritis In Patients With Joint Pain. American College of Rheumatology, Arthritis News [On-line press release]. Available online at http://www.rheumatology.org/press/2003/pr1.asp.
Bas, S. et. al. (2002). Diagnostic tests for rheumatoid arthritis: comparison of anti-cyclic citrullinated peptide antibodies, anti-keratin antibodies and IgM rheumatoid factors. Rheumatology 2002; 41: 809-814. [On-line journal]. Available online at http://rheumatology.oupjournals.org/cgi/content/full/41/7/809.
Vallbracht, I., et. al. (2004). Diagnostic and clinical value of anti-cyclic citrullinated peptide antibodies compared with rheumatoid factor isotypes in rheumatoid arthritis. Annals of the Rheumatic Diseases 2004;63:1079-1084. [On-line abstract]. Available online at http://ard.bmjjournals.com/cgi/content/abstract/63/9/1079.
Castelar Pinheiro, G., et. al. (2003 August 5). Anti–Cyclic Citrullinated Peptide Antibodies in Advanced Rheumatoid Arthritis. Annals of Internal Medicine, Letter, Volume 139 Issue 3, Pages 234-235. [On-line journal]. Available online at http://www.annals.org/cgi/content/full/139/3/234-a.
(©2004). 0055256: Cyclic Citrullinated Peptide Antibody, IgG. ARUP's User's Guide [On-line test information]. Available online at http://www.aruplab.com/guides/ug/tests/0055256.jsp.
Rauscher, M. (2003 October 28, Updated). Antibodies may help predict rheumatoid arthritis. MedicineNet.com, Reuters Health [On-line information]. Available online at http://www.medicinenet.com/script/main/art.asp?articlekey=25015.
Douglas, D. (2004 September 21). Antibodies Predict Course of Early Arthritis. MedlinePlus Health Information from Reuters [On-line news, not available after 10/21/2004]. Available online at http://www.nlm.nih.gov/medlineplus/news/fullstory_20221.html.
Schellekens, G., et. al., (1998 January). Citrulline is an Essential Constituent of Antigenic Determinants Recognized by Rheumatoid Arthritis-specific Autoantibodies. J. Clin. Invest. Volume 101, Number 1, January 1998, 273-281 [On-line journal]. Available online at http://www.jci.org/cgi/content/abstract/101/1/273.
Dina Dadabhoy, M.D., University of Michigan, Division of Rheumatology.
Pagana, Kathleen D. & Pagana, Timothy J. (© 2007). Mosby’s Diagnostic and Laboratory Test Reference 8th Edition: Mosby, Inc., Saint Louis, MO. Pp 73-74.
Wu, A. (2006). Tietz Clinical Guide to Laboratory Tests, Fourth Edition. Saunders Elsevier, St. Louis, Missouri. Pp 326.
Kelly, J. (2005 February 25). Anti-CCP plus RF may help find patients in the "treatment-window" stage of early RA. Medscape Medical News [On-line information]. Available online at http://www.medscape.com/viewarticle/538139. Accessed on 8-26-08.
van der Helm-van Mil, A. et. al. (2005 June 30). Antibodies to Citrullinated Proteins and Differences in Clinical Progression of Rheumatoid Arthritis. Medscape from Arthritis Res Ther. 2005;7(5):R949-R958 [On-line information]. Available online at http://www.medscape.com/viewarticle/507248. Accessed on 8-26-08.
Smith, H. (2006 May 24, Updated). Rheumatoid Arthritis. eMedicine [On-line information]. Available online at http://www.emedicine.com/med/TOPIC2024.HTM. Accessed on 8-26-08.
Emery, P. et. al. (2008 May 12). Clinical Identification and Treatment of a Rapidly Progressing Disease State in Patients With Rheumatoid Arthritis. Medscape from Rheumatology. 2008;47(4):392-398 [On-line information]. Available online at http://www.medscape.com/viewarticle/573156. Accessed on 8-26-08.
Fox, D. (2008 July 30). The ACR-EULAR Collaboration: An Expert Interview With David A. Fox, MD. Medscape Rheumatology [On-line information]. Available online at http://www.medscape.com/viewarticle/577523. Accessed on 8-26-08.
Niemeier, L. (2008 March 3). The Role of Anti-CCP in the Laboratory Diagnosis of Rheumatoid Arthritis. CAP Newspath [On-line information]. Available online through http://www.cap.org. Accessed on 8-26-08.
(© 2003). The Use of Anti-cyclic Citrullinated Peptide (anti-CCP) Antibodies in RA. American College of Rheumatology [On-line information]. Available online at http://www.rheumatology.org/publications/hotline/1003anticcp.asp. Accessed on 8/26/08.
Makover, M. (Updated 2011 February 14). Rheumatoid arthritis. MedlinePlus Medical Encyclopedia [On-line information]. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/000431.htm. Accessed January 2012.
(Updated 2011 August). Rheumatoid Arthritis. ARUP Consult [On-line information]. Available online at http://www.arupconsult.com/Topics/RA.html?client_ID=LTD. Accessed January 2012.
Temprano, K. and Smith, H. Updated 2011 December 29). Rheumatoid Arthritis. Medscape Reference [On-line information]. Available online at http://emedicine.medscape.com/article/331715-overview. Accessed January 2012.
(© 1995-2012). Mayo Clinic Mayo Medical Laboratories [On-line information]. Available online at http://www.mayomedicallaboratories.com/test-catalog/Overview/84182. Accessed January 2012.
(Updated 2011 September). Questions and Answers about Arthritis and Rheumatic Diseases. National Institute of Arthritis and Musculoskeletal and Skin Diseases [On-line information]. Available online at http://www.niams.nih.gov/Health_Info/Arthritis/arthritis_rheumatic_qa.asp. Accessed January 2012.
Aletaha, D. et. al. (2010 September). 2010 Rheumatoid Arthritis Classification Criteria, An American College of Rheumatology/European League Against Rheumatism Collaborative Initiative Arthritis & Rheumatism Vol. 62, No. 9, September 2010, pp 2569–2581 [On-line information]. Available online at http://www.rheumatology.org/practice/clinical/classification/ra/2010_revised_criteria_classification_ra.pdf#search=%22CCP%22. Accessed January 2012.
Pagana, K. D. & Pagana, T. J. (© 2011). Mosby's Diagnostic and Laboratory Test Reference 10th Edition: Mosby, Inc., Saint Louis, MO. Pp 76-77.
Henry's Clinical Diagnosis and Management by Laboratory Methods. 21st ed. McPherson R, Pincus M, eds. Philadelphia, PA: Saunders Elsevier: 2007, Pp 922-923.
(August 1, 2011) Center for Disease Control and Prevention. Rheumatoid Arthritis. Available online at http://www.cdc.gov/arthritis/basics/rheumatoid.htm. Accessed February 2012.
(Updated December 2011) American College of Rheumatology. Rheumatoid Arthritis, Who gets rheumatoid arthritis? Available online at http://www.rheumatology.org/practice/clinical/patients/diseases_and_conditions/ra.asp. Accessed March 2012.
Reviewer May 2015 Erin Kaleta, PhD, DABCC, Clinical Director, Sonora Quest Laboratories.
(October 2003) Kavanaugh, A., Matteson, E., Cush, J. The Use of anti-cyclic citrullinated peptide (anti-CCP) antibodies in RA, Hotline from the American College of Rheumatology. Available online at https://www.rheumatology.org/publications/hotline/1003anticcp.asp. Accessed on May 11, 2015.
Tietz Textbook of Clinical Chemistry and Molecular Diagnostics, 5th ed. Curtis, C.A., Ashwood, E.R., Bruns, D.E., eds. St. Louis: Elsevier Saunders.
Aletaha, D., Neogi, T., Silman, A.J., Funovitz, J., Felson, D.T., Bingham, C.O., et al. 2010 Rheumatoid Arthritis Classification Criteria. Arthritis & Rheumatism 62(9), 2569-2581.
Singh, J.A., Furst, D.E., Bharat, A., Curtis, J., Kavangaugh, A.F., Kremer, J.M. 2012 Update of the 2008 American College of Rheumatology recommendations for the use of disease-modifying anti-rheumatic drugs and biologic agents in the treatment of rheumatoid arthritis. Arthritis Care & Research 64(5), 625-639.
Taylor, P.C., Maini, R.N. Clinically useful biologic markers in the diagnosis and assessment of outcome in rheumatoid arthritis. In: UpToDate, O’Dell, J.R., Romain, P.L., eds. UpToDate, Waltham, MA. Accessed on May 12, 2015.